The presence of organophosphate esters (OPE) in industrial and agricultural drain waters, spills, runoffs, and drifts, as well as OPE agent-based chemical munitions that may be released in case of warfare or terrorist attack, pose great risks to human health and the environment. The number of exposures to OPE due to pesticides and insecticides is estimated at some 3,000,000 per year, with the total number of deaths and casualties over 300,000 per year worldwide. Eyer, P. “The role of oximes in the management of organophosphorus pesticide poisoning,” Toxicol Rev. 2003, 22(3), 165-190. Numerous OPE pesticides, insecticides and warfare agents, such as sarin, soman, and VX, in addition to being carcinogenic, act as nerve poisons which may cause cumulative damage to the nervous system and liver. The primary mechanism of action of the OPEs is irreversible inhibition of acetylcholinesterases, resulting in the accumulation of the neurotransmitter acetylcholine at nerve synapses. Structures of the nerve poison sarin and a model analog used in this study, diisopropyl fluorophosphate (DFP), are given in FIG. 1.
Some of the first OPE decontaminating agents were oxidizers, such as bleaching powders. See Yang, Y. C. et al. Yang, Y. C.; Baker, J. A.; Ward, J. R. “Decontamination of chemical warfare agents,” Chem. Rev. 1992, 92(8), 1729-1743. However, it has been observed that the activity of bleaches decreases upon long-term storage; to have the desired effect, copious amounts of bleach must be used. Moreover, because bleaches are quite corrosive, they are not compatible with many surfaces.
At present, the decontamination solutions of choice are DS-2 (a non-aqueous liquid composed of diethylenetriamine, ethylene glycol, monomethyl ether, and sodium hydroxide) and STB (super tropical bleach). Although DS-2 is generally not corrosive to metal surfaces, it damages skin, paints, plastics, rubber, and leather materials. STB, while effective, has the same environmental problems as bleaches and cannot be used on the skin. Consequently, personal decontamination equipment typically consists of packets of wipes containing such chemicals as sodium hydroxide, ethanol, and phenol. These chemicals are selected to provide a nucleophilic attack at the phosphorous atom of nerve agents.
Alternatives to oxidizers have focused on the development of processes for the catalytic destruction (CD) of nerve agents and pesticides. Chiron, S. et al. “Pesticide chemical oxidation: state-of-the-art,” Water Research 2000, 34(2), 366-377; and Russell, A. J. et al. “Biomaterials for mediation of chemical and biological warfare agents,” Annu. Rev. Biomed. Eng. 2003, 5, 1-27. It was first recognized in the 1950s that certain metal ions, especially Cu(II), had the ability to catalyze the hydrolysis of nerve agents and their simulants. The catalytic activity of such chemicals was significantly enhanced when Cu(II) was bound to certain ligands. For example, diisopropyl phosphorofluoridate (DFP) has a hydrolytic half-life of approximately 2 days in water, 5 hours in water when CUSO4 is added, and just 8 minutes in water when Cu(II) bound to either histidine or N,N′-dipyridyl is added in an approximately 2:1 ratio of metal complex to substrate. Sarin was found to be even more susceptible to metal-based catalysis with a half-life of only 1 minute in the presence of tetramethyl-EDA-Cu(II) complex (1:1 metal complex to substrate). However, the use of free copper-ligand complexes for catalyzing the degradation of nerve agents also has disadvantages. First, the nerve agent must be brought into contact with a solution of the metal-ion-containing catalyst. Second, the ratio of metal to chelate must be carefully controlled. Third, solubility issues can still limit the pH range and choice of chelates for use in a particular environment.
In addition, researchers have begun to look at enzymes stabilized by attachment to polymeric support as catalysts for the degradation of nerve agents. These enzymes, variously known as organophosphorous acid anhydrases, phosphotriesterases, sarinase, or others, are extracted either from microorganisms, such as Pseudomonas diminuta, or from squid. The enzymatic approach shows promise but is limited by the specificity of the proteins for their substrates, e.g., a parathion hydrolase would not be effective against another nerve agent. Further, the enzymes require a very specific range of conditions, e.g., pH, to function properly. In addition, field conditions can involve concentrated solutions of nerve agents, which can overwhelm the relatively low concentration of enzymes which can be immobilized on a support.
The shortcomings of the free metal-ligand complexes and enzymatic approaches has caused the majority of the practical catalytic destruction technologies to focus on acid-catalyzed or base-catalyzed hydrolysis or nucleophile-aided hydrolysis. Magee, R. S. “U.S. chemical stockpile disposal program: the search for alternative technologies. In Effluents From Alternative Demilitarization Technologies,” ed. F W Holm, Dordrecht: Kluwer Acad., 1998, 22, 112; Amos, D.; Leake, B. “Clean-up of chemical agents on soils using simple washing or chemical treatment processes,” J. Hazard. Mater. 1994, 39, 107 17; Yang, Y. C. “Chemical detoxification of nerve agent,” Acc. Chem. Res. 1999, 32, 109-15; and Yang, Y. C.; Baker, J. A.; Ward, J. R. “Decontamination of chemical warfare agents,” Chem. Rev. 1992, 92(8), 1729-1743. In this regard, α-nucleophiles, such as hydroperoxides, hypochlorite, iodosocarboxylates and oximates, have been investigated alone or in concert with surfactants. Wagner, G. W.; Yang, Y.-C. “Rapid Nucleophilic/Oxidative Decontamination of Chemical Warfare Agents,” Ind. Eng. Chem. Res. 2002, 41(8), 1925-1928; Moss, R. A.; Chung, Y. C. “Immobilized iodosobenzoate catalysts for the cleavage of reactive phosphates,” J. Org. Chem. 1990, 55(7), 2064-2069; and Fanti, M.; Mancin, F.; Tecilla, P.; Tonellato, U. “Ester Cleavage Catalysis in Reversed Micelles by Cu(II) Complexes of Hydroxy-Functionalized Ligands,” Langmuir 2000, 16(26), 10115-10122. However, very few reagents are currently available that are both inexpensive and non-toxic as well as catalytic. Rather, most of these compounds show only stoichiometric dephosphorylating activities at neutral pH. Bhattacharya, S.; Snehalatha, K. “Evidence for the Formation of Acylated or Phosphorylated Monoperoxyphthalates in the Catalytic Esterolytic Reactions in Cationic Surfactant Aggregates,” J. Org. Chem. 1997, 62(7), 2198-2204. Notable exceptions include micellar iodosobenzoate, and related derivatives, micelle-forming metallocomplexes, and immobilized metal chelate complexes. Moss, R. A.; Chung, Y. C. “Immobilized iodosobenzoate catalysts for the cleavage of reactive phosphates,” J. Org. Chem. 1990, 55(7), 2064-2069; Menger, F. M.; Gan, L. H.; Johnson, E.; Durst, D. H. “Phosphate ester hydrolysis catalyzed by metallomicelles,” J. Amer. Chem. Soc. 1987, 109(9), 2800-2803; and Chang et al. (US 2003/0054949 A1).